The skin is constructed by the outer thin epidermis (epithelium tissue) that forms the outermost layer of the body, protects living bodies from the outside world, and plays a role of preventing the body moisture and nutrients from escaping from the body; and the thick dermis (connective tissue) that has a complexly, three-dimensionally extending structure of fibroblasts, collagen fibers, elastic fibers, proteoglycans, etc., mainly. Skin conditions are maintained by the epidermis and the dermis while keeping their respective normal tissue structures and physiological functions.
The epidermis of the skin is classified into “stratum basale”, “stratum spinosum”, “stratum granulosum”, and “stratum corneum”, from the side of the dermis, and is mainly composed of cells called keratinocytes. Such keratinocytes form a monolayer as immature cells with proliferating ability in the undermost layer stratum basale, differentiate (keratinization) while proliferating and growing and being boosted toward the upper layer, and finally turn into corneocytes as death cells with no nuclei for forming stratum corneum, which are then sequentially desquamated from the surface layer part of the stratum corneum. Cutaneous homeostasis is maintained by a constantly-cyclic-smooth-turnover of a process of proliferation, passage, differentiation, and desquamation of keratinocytes in the epidermis of the skin.
The skin, however, is deteriorated to lose its moisture by different factors such as ageing, drying, oxidation, and sunlight (ultraviolet rays), resulting in showing various phenomena such as the generation of wrinkles and sagging skin and the reduction of skin firmness and elasticity. One of the main causatives of such skin deterioration has been recognized as the reduction of collagen synthesis by fibroblasts to lower the collagen level in the dermis; there have been explored various external dermal agents and food products, in which incorporated collagen or agents for augmenting collagen production to improve the reduction of collagen level (see, for example, Japanese Patent No. 3495217 and Japanese Patent Kokai No. 2007-186471).
In the epidermis that constitutes the outermost layer of the body, undesirable conditions that would be factors for inducing wrinkles may be induced: As the inhibition of the proliferation and the differentiation of keratinocytes that constitute the epidermis, supplying of corneocytes from the lower layer and forming of keratinous layer in the upper layer are reduced; the thickening and the moisture reduction or the like in the keratinous layer are induced by the interruption of turnover of keratinous layer; and the moisturizing- and barrier-functions of keratinous layer are lowered. When the drying in the skin proceeds due to a relatively low-humid environment, excessive skin-washing, ageing, constitution, etc., multiple peeling of keratinous layer becomes to be easily induced and to cause drawbacks such as the reduction of skin gloss and the deterioration of smooth makeup, as well as inducing skin troubles such as the generation of wrinkles, rough skin, etc. To improve such skin troubles, trials for enhancing the proliferation and the differentiation of keratinocytes have been made, and compositions for use in the skin, into which substances capable of enhancing the differentiation of keratinocytes are incorporated, have been proposed (see, for example, Japanese Patent Application Prior-to-Examination Publication (Tokuhyo) Nos. 2001-510777 and 507289/96).
As described above, various substances, which improve the deterioration of skin conditions including the generation of wrinkles, i.e., which improves the reduction of collagen-producing ability in the dermis and the deterioration of the turnover of keratinous layer in the epidermis, and compositions used for the skin have been variously proposed. Since all the above concern only on the improvement of the symptom of the epidermis or the dermis, their anti-wrinkle actions are not successfully satisfactory. Accordingly, there has been desired a development of an external dermal agent that improves the symptoms in both the epidermis and the dermis, keeps comprehensively cutaneous homeostasis, and imparts a high anti-wrinkle action. Japanese Patent Kokai No. 2009-149557 discloses prolactin, as an example of substances having the above functions, which has drawbacks, due to its nature of a peptide, in stability, permeability into the stratum basale, etc., when formulated into preparations or applied to the skin as an external agent. To overcome these drawbacks, there have been eagerly anticipated a novel ingredient that has a satisfactory anti-wrinkle action through its action on both the epidermis and the dermis and also has an improved sustainable effect, and an external dermal agent with such an ingredient.